RATIONALE AND OBJECTIVES: We previously found time dependent increases, or incubation, of cocaine seeking induced by re-exposure to cocaine cues over withdrawal periods of up to 3 months. Here, we studied cocaine seeking induced by re-exposure to cocaine cues or cocaine itself over an extended withdrawal period of 6 months. METHODS: Rats were trained to self-administer intravenous cocaine for 6 h/day for 10 days. Cocaine seeking induced by re-exposure to cocaine cues or cocaine itself, as measured in extinction or drug-induced reinstatement tests, respectively, was then assessed 1 day, or 1, 3 or 6 months after withdrawal. Rats were first given six 1-h extinction sessions wherein lever presses resulted in contingent presentations of cues previously paired with cocaine infusions. Subsequently, reinstatement of drug seeking induced by cocaine injections (expt 1: 0, 5, and 15 mg/kg, i.p.; expt 2: 0, 2.5, and 5 mg/kg) was assessed during three 1-h sessions. RESULTS: Profound time dependent changes in responsiveness to cocaine cues in the extinction tests were observed, with low responding after 1 day, high responding after 1 and 3 months, and intermediate responding after 6 months of withdrawal. In contrast, no significant time dependent changes in cocaine-induced drug seeking were found; acute re-exposure to cocaine effectively reinstated responding at all withdrawal periods. CONCLUSIONS: Results indicate that the withdrawal period is a critical modulator of drug seeking provoked by re-exposure to cocaine cues, but not cocaine itself. Results also indicate that while the incubation of responsiveness to cocaine cues is a long lasting phenomenon, it is not permanent.
RATIONALE AND OBJECTIVES: We previously found time dependent increases, or incubation, of cocaine seeking induced by re-exposure to cocaine cues over withdrawal periods of up to 3 months. Here, we studied cocaine seeking induced by re-exposure to cocaine cues or cocaine itself over an extended withdrawal period of 6 months. METHODS:Rats were trained to self-administer intravenous cocaine for 6 h/day for 10 days. Cocaine seeking induced by re-exposure to cocaine cues or cocaine itself, as measured in extinction or drug-induced reinstatement tests, respectively, was then assessed 1 day, or 1, 3 or 6 months after withdrawal. Rats were first given six 1-h extinction sessions wherein lever presses resulted in contingent presentations of cues previously paired with cocaine infusions. Subsequently, reinstatement of drug seeking induced by cocaine injections (expt 1: 0, 5, and 15 mg/kg, i.p.; expt 2: 0, 2.5, and 5 mg/kg) was assessed during three 1-h sessions. RESULTS: Profound time dependent changes in responsiveness to cocaine cues in the extinction tests were observed, with low responding after 1 day, high responding after 1 and 3 months, and intermediate responding after 6 months of withdrawal. In contrast, no significant time dependent changes in cocaine-induced drug seeking were found; acute re-exposure to cocaine effectively reinstated responding at all withdrawal periods. CONCLUSIONS: Results indicate that the withdrawal period is a critical modulator of drug seeking provoked by re-exposure to cocaine cues, but not cocaine itself. Results also indicate that while the incubation of responsiveness to cocaine cues is a long lasting phenomenon, it is not permanent.
Authors: Hanbing Lu; Svetlana Chefer; Pradeep K Kurup; Karine Guillem; D Bruce Vaupel; Thomas J Ross; Anna Moore; Yihong Yang; Laura L Peoples; Elliot A Stein Journal: Neuroimage Date: 2012-06-01 Impact factor: 6.556
Authors: Mikko Airavaara; Charles L Pickens; Anna L Stern; Kristina A Wihbey; Brandon K Harvey; Jennifer M Bossert; Qing-Rong Liu; Barry J Hoffer; Yavin Shaham Journal: Addict Biol Date: 2010-12-23 Impact factor: 4.280
Authors: Irina N Krasnova; Nathan J Marchant; Bruce Ladenheim; Michael T McCoy; Leigh V Panlilio; Jennifer M Bossert; Yavin Shaham; Jean L Cadet Journal: Neuropsychopharmacology Date: 2014-03-03 Impact factor: 7.853
Authors: Xuan Li; M R DeJoseph; Janice H Urban; Amine Bahi; Jean-Luc Dreyer; Gloria E Meredith; Kerstin A Ford; Carrie R Ferrario; Jessica A Loweth; Marina E Wolf Journal: J Neurosci Date: 2013-01-16 Impact factor: 6.167